Foci of necrosis are generally originate in cell death induced in a state that supply of nutrition and oxygen to cells of various tissues is reduced due to physical injury or obstruction, loss or reduction of blood supply. For example, in the case of solid carcinomas, when a carcinoma grows, supply of nutrition no longer spread over the whole carcinoma tissue, and as a result, a focus of necrosis is generated. Further, myocardial infarction and cerebral infarction are always accompanied by necrosis. Furthermore, postnecrotic cirrhosis, and necrotizing pancreatitis, in which oligotrophy and hypoxia are induced by mal blood flow, as well as necrotizing fasciitis, which is inflammation to be aggravated in subcutaneous tissues to the fascia, and so forth are also pathological conditions accompanied by foci of necrosis. In addition, arteriosclerotic gangrene, diabetic gangrene, and obstructive gangrene are also diseases relating to foci of necrosis.
Since foci of necrosis badly influence on surrounding tissues and cells, if it becomes possible to detect or diagnose condition or lesion of a necrosis part, or find such an aggravated lesion and perform a therapeutic treatment for that lesion as a target, it will be industrially useful.
However, prior art techniques concerning biomarkers for detecting a focus of necrosis are limited to the three kinds of antibodies selected by using insoluble intracellular antigens derived from a lymphoma cell line or lung cancer cell line (Patent document 1), an antibody against a soluble nuclear matrix protein (Patent document 2), an antibody or low molecular weight antibody specifically binding to the nucleus extract identified as a center of necrosis of a tumor and histone H1 (Patent document 3), and so forth. As markers for diagnosing severity including necrosis of a cardiovascular diseases-related tissue, inflammatory markers (CRP, TNF, IL-1, IL-6 etc.) are known. BNP is also used as a myocardial stress marker.
Further, as biomarkers of carcinomas, for example, peroxiredoxin 4 is known as a biomarker of pancreatic cancer and lung adenocarcinoma (Non-patent documents 1 and 2), and annexin A2 is known as a biomarker of large intestine carcinoma (Patent document 4). Furthermore, development of specific monoclonal antibodies against HMGB1, which is released from cell nuclei of necrotic cells, for use in therapeutic treatment is also advancing.